We have previously demonstrated that patients with chest pain and normal coronary angiograms commonly have exaggerated cardiac sensitivity, with their typical pain provoked by right ventricular pacing in the absence of ischemia. In order to asses the impact of drugs used in chronic neuropathic pain syndromes, we compared imipramine 50 mg, and clonidine .2 mg to placebo in a randomized trial in 30 patients, with a one month placebo trial (single blind) for all patients followed by a one month treatment period (double-blind) on imipramine, clonidine, or placebo (10 patients each group). Right ventricular pacing was repeated at the end of the second month treatment period. Compared to the first month on placebo, imipramine treated patients experienced a 57 +/- 27% (mean +/- SD) reduction in chest pain episodes (p=.05 by ANOVA) compared to a 21 +/- 72% reduction in chest pain in clonidine-treated patients and a 29 +/- 104% increase in chest pain for placebo-treated patients. Only imipramine-treated patients demonstrated a reduction in prevalence of chest pain provoked by right ventricular pacing, from 80% off all medications to 20% on imipramine (p<.03). Thus, imipramine in relatively low doses produces a reduction in chest pain frequency in patients with chest pain and normal coronary arteries, a response that may be a consequence of visceral analgesic effects of the drug.